Cancer is a term used to describe a group of malignancies that all share the common trait of developing when cells in a part of the body begin to grow out of control. Most cancers form as tumors, but can also manifest in the blood and circulate through other tissues where they grow. Cancer malignancies are most commonly treated with a combination of surgery, chemotherapy, and/or radiation therapy. The type of treatment used to treat a specific cancer depends upon several factors including the type of cancer malignancy and the stage during which it was diagnosed.
The chemotherapeutic agent whose common chemical name is thalidomide has the following formula:

The chemotherapeutic agent whose common chemical name is lenalidomide has the following formula:

Thalidomide possesses immunomodulatory, anti-inflammatory and anti-angiogenic properties. The immunomodulatory and anti-inflammatory properties may be related to suppression of excessive tumor necrosis factor-alpha production through degradation of mRNA encoding the factor (Moreira, J Exp Med, 177(6): 1675-80, 1993). Other immunomodulatory and anti-inflammatory properties of thalidomide may include suppression of macrophage involvement in prostaglandin synthesis, and modulation of interleukin-10 and interleukin-12 production by peripheral blood mononuclear cells. The combination of anti-inflammatory and anti-angiogenic properties makes thalidomide a novel therapeutic agent with significant potential in treating a wide variety of diseases (Teo, Clin Pharmacokinet, 43(5): 311-27, 2004). A number of recent clinical trials have demonstrated therapeutic effect of thalidomide in patients with multiple myeloma, renal carcinoma and glioblastoma multiforme (Singhal, N Engl J Med, 341(21): 1565-71, 1999; Marx, J Neurooncol, 54(1): 31-8, 2001). Currently, thalidomide is approved for treatment of patients with newly diagnosed multiple myeloma and for acute treatment of erythema nodosum leprosum (Package-insert-Thalidomide, Celgene Corp., 2009).
Lenalidomide is a thalidomide derivative with immunomodulatory, anti-proliferative, and anti-angiogenic properties. Lenalidomide exerts direct anti-proliferative effect on multiple myeloma cells by inducing cell cycle arrest and apoptosis (Armoiry, J Clin Pharm Ther, 33(3): 219-26, 2008). Lenalidomide is approved for treatment of patients with multiple myeloma and myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality (Package-insert-Revlimid, Celgene Corp., 2009).
The mechanisms of action and metabolic pathways of thalidomide and lenalidomide are not fully characterized yet. In vivo, both drugs can undergo non-enzymatic hydrolysis and enzymatic metabolism producing a multitude of metabolites, but none of those compounds were found to be responsible for thalidomide therapeutic effect Lepper, Curr Drug Metab, 7(6): 677-85, 2006).
Thalidomide and lenalidomide exhibit significant variability in plasma concentrations. A phase I study of pharmacokinetic effects of thalidomide in HIV patients has demonstrated a wide range of maximum drug concentration Cmax (2.8±2.6 mg/L) and half-life time t1/2 (5.9±2.3 hours) (Wohl, J Infect Dis, 185(9): 1359-63, 2002). Administration of thalidomide to healthy subjects resulted in up to 52% variability in Cmax and up to 37% variability in t1/2 (Package-insert-Thalidomide, Celgene Corp., 2009). A Phase I trial of lenalidomide in patients with central nervous system tumors has revealed up to 78% variability in Cmax and up to 122% variability in t1/2 (Fine, Clin Cancer Res, 13(23): 7101-6, 2007).
Since efficacy of thalidomide and lenalidomide is improved at higher concentration levels and the drugs exhibit wide intra- and inter-patient pharmacokinetic variability monitoring concentrations of these drugs in blood and adjusting to target levels would be of value in increasing efficacy and minimizing toxicity. The degree of intra- and inter-individual pharmacokinetic variability of thalidomide and lenalidomide is impacted by many factors, including:                Age        Weight        Organ function        Drug-drug interaction        Genetic regulation        Compliance        
As a result of this variability, equal doses of the same drug in different individuals can result in dramatically different clinical outcomes. The effectiveness of the same dosage of thalidomide and lenalidomide varies significantly based upon individual drug clearance and the ultimate serum drug concentration in the patient. Therapeutic drug management would provide the clinician with insight on patient variation in drug administration. With therapeutic drug management, drug dosages could be individualized to the patient, and the chances of effectively treating the disorder without the unwanted side effects would be much higher.
Routine therapeutic drug management of thalidomide and lenalidomide would require the availability of simple automated tests adaptable to general laboratory equipment. The use of liquid chromatography (LC) with UV or mass spectroscopy detection to determine the concentration of thalidomide and lenalidomide in human blood and plasma has been described (Tohnya, J Chromatogr B Analyt Technol Biomed Life Sci, 811(2): 135-41, 2004; Chen, J Clin Pharmacol, 47(12): 1466-75, 2007; Teo, J Clin Pharmacol, 39(11): 1162-8, 1999). These methods are labor intensive, requiring liquid-liquid or solid phase extractions, use expensive equipment and are not amenable to routine clinical laboratory use. To date, there are no immunoassays for measuring lenalidomide and/or thalidomide in human biological fluids of patients treated with these chemotherapeutic agents.
As seen from the foregoing, there are no immunoassays for determining the presence and/or quantifying the amount of thalidomide and lenalidomide in human biological fluids. Routine therapeutic drug management of thalidomide and lenalidomide by immunoassays would provide simple automated tests adapted to standard laboratory equipment. However, in order to provide such immunoassays, antibodies specific to thalidomide and lenalidomide must be produced. The derivatives and immunogen used in this assay must impart through these corresponding antibodies produced specific reactivity to thalidomide and lenalidomide.